162536-45-0

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 587-33-7 m-tyrosine 
• 100-39-0 benzyl bromide 
• 90819-30-0 (S)-2-((tert-butoxycarbonyl)amino)-3-(3-hydroxyphenyl)propanoic acid 

Downstream Products

• 162538-23-0 [(S)-1-(3-Benzyloxy-benzyl)-3-((S)-3-tert-butoxycarbonylamino-2-hydroxy-4-phenyl-butylamino)-2-hydroxy-propyl]-carbamic acid tert-butyl ester 
• 162538-24-1 [(S)-3-((S)-3-tert-Butoxycarbonylamino-2-hydroxy-4-phenyl-butylamino)-2-hydroxy-1-(3-hydroxy-benzyl)-propyl]-carbamic acid tert-butyl ester 
• 1026869-14-6 [(S)-1-(3-Benzyloxy-benzyl)-3-chloro-2-oxo-propyl]-carbamic acid tert-butyl ester 
• 162536-46-1 (S)-3-(3-(benzyloxy)phenyl)-2-((tert-butoxycarbonyl)amino)propanoic acid 

Relevant academic research and scientific papers

METHODS AND REAGENTS FOR ANALYZING PROTEIN-PROTEIN INTERFACES

The present disclosure provides methods and reagents useful for analyzing protein-protein interfaces such as interfaces between a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein. In some embodiments, the target and/or presenter proteins are intracellular proteins. In some embodiments, the target and/or presenter proteins are mammalian proteins.

Constraining the Side Chain of C-Terminal Amino Acids in Apelin-13 Greatly Increases Affinity, Modulates Signaling, and Improves the Pharmacokinetic Profile

Side-chain-constrained amino acids are useful tools to modulate the biological properties of peptides. In this study, we applied side-chain constraints to apelin-13 (Ape13) by substituting the Pro12 and Phe13 positions, affecting the binding affinity and signaling profile on the apelin receptor (APJ). The residues 1Nal, Trp, and Aia were found to be beneficial substitutions for Pro12, and the resulting analogues displayed high affinity for APJ (Ki 0.08-0.18 nM vs Ape13 Ki 0.7 nM). Besides, constrained (d-Tic) or α,α-disubstituted residues (Dbzg; d-α-Me-Tyr(OBn)) were favorable for the Phe13 position. Compounds 47 (Pro12-Phe13 replaced by Aia-Phe, Ki 0.08 nM) and 53 (Pro12-Phe13 replaced by 1Nal-Dbzg, Ki 0.08 nM) are the most potent Ape13 analogues activating the Gα12 pathways (53, EC50 Gα12 2.8 nM vs Ape13, EC50 43 nM) known to date, displaying high affinity, resistance to ACE2 cleavage as well as improved pharmacokinetics in vitro (t1/2 5.8-7.3 h in rat plasma) and in vivo.

Compounds participating in cooperative association and uses thereof

The invention features compounds (e.g., macrocyclic compounds) capable of modulating biological processes, for example through binding to a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein (e.g., a eukaryotic target protein such as a mammalian target protein or a fungal target protein or a prokaryotic target protein such as a bacterial target protein). These compounds bind endogenous intracellular presenter proteins, such as the FKBPs or cyclophilins, and the resulting binary complexes selectively bind and modulate the activity of intracellular target proteins. Formation of a tripartite complex among the presenter protein, the compound, and the target protein is driven by both protein-compound and protein-protein interactions, and both are required for modulation of the targeted protein's activity.

MACROCYCLIC COMPOUNDS AS PROTEASOME INHIBITORS

The compounds of the present invention are represented by the following compounds having Formula I and Formula (I'): where the substituents R1, R2, R2', R3, R4, R5, R', R", X, Y, and Z are as defined herein and where the substituents R1, R2, R3, R4, R5, R', R", X, Y, and Z are as defined herein. These compounds are used in the treatment of bacterial infections, parasite infections, fungal infections, cancer, immunologic disorders, autoimmune disorders, neurodegenerative diseases and disorders, inflammatory disorders, or muscular dystrophy or for providing immunosuppression for transplanted organs or tissues.

Aminodiol HIV protease inhibitors. Synthesis and structure - Activity relationships of P1/P1′ compounds: Correlation between lipophilicity and cytotoxicity

A series of novel aminodiol inhibitors of HIV protease based on the lead compound 1 with structural modifications at P1′ were synthesized in order to reduce the cytotoxicity of 1. We have observed a high degree of correlation between the lipophilicity and the cytotoxicity of this series of inhibitors. It was found that appropriate substitution at the para position of the P1′ phenyl group of 1 resulted in the identification of equipotent (both against the enzyme and in cell culture) compounds (101, 10m, 10n, and 15c) which possess significantly decreased cytotoxicity.